1. Field of the Invention
The subject matter disclosed generally relates to a detector that can detect trace molecules.
2. Background Information
There have been developed high-speed methods of sequencing molecular structure using a mass spectrometer and methods of applying excitation waveforms to specific ion masses. These methods belong to a class of sequential mass spectrometry analysis often referred to as MS/MS and MSn. There have also been developed mass spectrometers that utilize an ion trap. The ion trap was originally invented by Paul and Stenwedel and was disclosed in U.S. Pat. No. 2,939,952. The ability to store ions and then scan them out in sequence of mass was developed by Stafford et al. and was disclosed in U.S. Pat. No. 4,540,884. Lubman published the first QitTof MS method. It used the ion trap to collect the ions in the usual manner, but analyzed the masses by pulsing the ions into a time-of-flight mass spectrometer. Syage et al. disclosed in U.S. Pat. No. 6,326,615 a QitTof MS apparatus that uses a discharge ionizer and a photoionizer.
Another useful characteristic of ion traps is the ability to apply an oscillating potential or waveform to match the frequency of a specific ion mass. The waveform excites the ions to higher kinetic energy. If driven strongly, ions of a specific mass can be made to exit the trap either to detect it or to remove it from further analysis. If driven less strongly, these ions can undergo energetic collisions in the ion trap with background gas causing them to dissociate. This process is very useful for determining the structure of the ion. Armitage et al in 1979 disclosed a method of resonant ejection of ions. Syka et al. disclosed in U.S. Pat. No. 4,736,101 a method in which the trapping field is scanned to eject unwanted ions and then changed again so that the expected daughter ions from dissociation of the remaining parent ions are stable. More sophisticated methods have been developed. Marshall et al. disclosed in U.S. Pat. No. 4,761,545 a method call tailored waveform excitation which was based on determining the frequency spectrum needed to effect excitation and then generating an inverse Fourier transform to convert the frequency spectrum into a complex waveform in the time domain. Kelley disclosed in U.S. Pat. No. 5,206,507 a method of generating a broadband noise spectrum with a notch or notches to trap one or more desired masses, while ejecting the remaining masses.
Louris has described a sum of sine method for the resonant ejection of ions in a quadrupole ion trap or an ion cyclotron resonance mass spectrometer in U.S. Pat. No. 5,324,939. The method disclosed by Louris, however does not describe a method by which such sum of sine waveforms are used to implement MS/MS nor MSn for the purpose of structure elucidation. Lubman published a demonstration of MS/MS in a QitTof MS.
A principal benefit of QitTof MS compared to ITMS is the ability to record MS spectra at high speeds. Both the QitTof MS and ITMS methods are based on an accumulation of ions in an ion trap followed by ion mass analysis of the stored ions. In ITMS the stored ions are scanned out by the general method of mass-selective instability scan. There are several specific methods for scanning the ions; however, they are all based on the general principle of destabilizing ions of increasing mass so that they escape the ion trap and are detected by an external ion detector. If we assume a scan rate of 10,000 amu/s and a total scan range of 1000 amu, then the total scan time is 100 ms. Because injection of ions into the ion trap is avoided during this scan period, the repeat time for ion collection and scan out must be greater than 100 ms in order to have an adequate duty cycle for collection of ions. For a 50% duty cycle for collection and scan out, the maximum repetition rate of the ITMS would be 5 Hz.
The QitTof MS uses an external TOFMS for ion mass analysis. Ions that have accumulated in the ion trap are pulsed out into the TOFMS in about 10 microseconds. During the pulse out time the radiofrequency that is applied to the ion trap to store the ions is switched off. This time and the additional time for the RF to recover to a stable voltage represents the time when ion injection into the ion trap is halted. This is generally about 100-500 microseconds, which is considerably shorter than the 100 ms for the ITMS instrument. Consequently, QitTof MS can operate at much higher repetition rates and still maintain high duty cycles for ion collection.
High speed analysis is important for several reasons. First, advances in drug discovery, genomics and proteomics are creating the need to conduct analyses of ever increasing numbers of samples. Second, chromatographic techniques, such as liquid chromatography (LC) and capillary electrophoresis (CE), which are frequently used to separate the constituents of these mixtures, are being developed to operate with increasing speeds. Each constituent may elute from chromatography columns in very short time, such as less than 1 second. This requires analyzers that sample the eluting peak sufficiently often to reliably reproduce the transient signal. ITMS may not meet this requirement in many cases where QitTof MS would.